Excitatory amino acids such as glutamate can profoundly stimulate the reproductive axis of primates by promoting the release of gonadotropin-releasing hormone (GnRH). Our research has been aimed at elucidating the distribution and developmental regulation of glutamate receptor subunits within the macaque brain, especially in those areas associated with the GnRH neural circuits. Using immunohistochemistry (IHC) and in situ hybridization (ISH), we have now completed a comprehensive distribution study of the major ionotropic glutamate receptor subunits, and corresponding mRNA, in the hypothalamus, hippocampus, cerebral cortex, cerebellum and locus coeruleus. Moreover, we have initiated studies to examine how their expression is influenced by gonadal steroids. Using a combination of IHC and ISH, as well as double-label IHC, we have discovered that significant glutamate receptor gene expression occurs only in a specific subpopulation of GnRH neurons which are located in lateral regions of the hypothalamus and amygdala. They differ significantly from medially-located GnRH neurons in terms of their size, morphology and total GnRH mRNA content. Also, their number decreases markedly during the juvenile period of development, in association with the onset of a hiatus in GnRH secretion. Previously, only one molecular form of the GnRH neuropeptide was thought to exist in primates. We now have evidence supporting the existence of at least one alternate form, which based on preliminary sequencing studies corresponds to the chicken-II form that is commonly expressed in lower vertebrates and which has also recently been identified in humans. Current studies are using ISH to identify the subpopulations of GnRH neurons that express this novel molecular form of Gn2RH. Elucidation of how GnRH neurons are integrated with major neurotransmitters of the central nervous system is fundamental to the understanding of hypothalamic causes of human infertility and reproductive disorders such precocious and delayed puberty. Our studies should, therefore, help in the design of effective therapies and also provide new approaches for contraception.